tbuckley/cabot-search huggingface dataset:
Projected Savings for Generic Oncology Drugs Purchased via Mark Cuban Cost Plus Drug Company Versus in Medicare
Authors: Brian D. Cortese, Stacie B. Dusetzina, Amy N. Luckenbaugh, Bashir Al Hussein Al Awamlh, C.J. Stimson, Daniel A. Barocas, David F. Penson, Sam S. Chang, Ruchika Talwar
Journal: Journal of Clinical Oncology (2023)

Self-administered oncology drugs contribute disproportionately to Medicare Part D spending; prices often remain high even after generic entry. Outlets for low-cost drugs such as Mark Cuban Cost Plus Drug Company (MCCPDC) offer opportunities for decreased Medicare, Part D, and beneficiary spending. We estimate potential savings if Part D plans obtained prices such as those offered under the MCCPDC for seven generic oncology drugs.Using the 2020 Medicare Part D Spending dashboard, Q3-2022 Part D formulary prices, and Q3-2022 MCCPDC prices for seven self-administered generic oncology drugs, we estimated Medicare savings by replacing Q3-2022 Part D unit costs with costs under the MCCPDC plan.We estimate potential savings of $661.8 million (M) US dollars (USD; 78.8%) for the seven oncology drugs studied. Total savings ranged from $228.1M USD (56.1%) to $2,154.5M USD (92.4%) compared with 25th and 75th percentiles of Part D plan unit prices. The median savings replacing Part D plan prices were abiraterone $338.0M USD, anastrozole $1.2M USD, imatinib 100 mg $15.6M USD, imatinib 400 mg $212.0M USD, letrozole $1.9M USD, methotrexate $26.7M USD, raloxifene $63.8M USD, and tamoxifen $2.6M USD. All 30-day prescription drug prices offered by MCCPDC generated cost savings except for three drugs offered at the 25th percentile Part D formulary pricing: anastrozole, letrozole, and tamoxifen.Replacing current Part D median formulary prices with MCCPDC pricing could yield significant savings for seven generic oncology drugs. Individual beneficiaries could save nearly $25,200 USD per year for abiraterone or between $17,500 USD and $20,500 USD for imatinib. Notably, Part D cash-pay prices for abiraterone and imatinib under the catastrophic phase of coverage were still more expensive than baseline MCCPDC prices.
Prostate-Specific Membrane Antigen Uptake Heterogeneity in Mixed Ductal-Acinar Adenocarcinoma of the Prostate
Authors: Qian Zhao, Aisheng Dong, Yushu Bai, Changjing Zuo
Journal: Clinical Nuclear Medicine (2023)

Abstract Prostate-specific membrane antigen (PSMA) PET findings of mixed ductal-acinar adenocarcinoma of the prostate are rarely reported. We describe 18 F-PSMA-1007 PET/CT and delayed pelvic 18 F-PSMA-1007 PET/MRI findings in a case of prostatic mixed ductal-acinar adenocarcinoma with multiple lymph node and bone metastases. The primary tumor showed heterogeneous PSMA uptake. The metastases in the right ilium and acetabulum showed intense PSMA uptake, but the pelvic lymph node and left iliac bone metastases showed no significant PSMA uptake. Knowledge of the intraprimary and intermetastatic heterogeneity of PSMA uptake in mixed ductal-acinar adenocarcinoma of the prostate may be helpful for accurate interpretation.
Corrigendum to “SMO-CRISPR-mediated apoptosis in CD133 targeted cancer stem cells and tumor growth inhibition” [Journal of Controlled Release, Volume 357 (2023) 94–108/COREL_12113]
Authors: Shambhavi Pandey, Myung Chul Lee, Jaewoon Lim, Sangbae Park, Yun-Hoon Choung, Jae Eun Kim, Pankaj Garg, Jong Hoon Chung
Journal: Journal of Controlled Release (2023)
Anti-tumor activity of sunvozertinib in NSCLC with EGFR sensitizing mutations after failure of EGFR TKI treatment.
Authors: James Chih-Hsin Yang, Yan Xu, Wen-Tsung Huang, Wu-Chou Su, Bo Gao, Chee Khoon Lee, Jian Fang, Wenlei Yu, Mengzhao Wang, Pasi A. Janne
Journal: Journal of Clinical Oncology (2023)

9103 Background: Sunvozertinib is a rationally designed, irreversible EGFR inhibitor targeting various EGFR mutations with wild-type EGFR selectivity. Clinical studies have showed its superior efficacy than current available therapies and favorable safety profile for treating NSCLC patients with EGFR exon20 mutations. Here we reported its anti-tumor activity in patients with EGFR sensitizing mutations (EGFRm) who failed from standard EGFR TKI treatment. Methods: This is a pooled analysis of three clinical studies in patients with EGFRm or HER2m NSCLC: WU-KONG1 (multinational phase I/II study, NCT03974022), WU-KONG2 (phase I study in China, CTR20192097), and WU-KONG15 (phase II study in China, NCT05559645). Patients were enrolled to receive sunvozertinib once daily at defined doses until discontinuation criteria were met. Patients who had EGFRm NSCLC, at least one measurable lesion at baseline, received at least one dose of sunvozertinib, and underwent at least one post-treatment RECIST assessment were evaluable for efficacy analysis. Patients with EGFRm or HER2m NSCLC who failed from standard systemic therapies and received at least one dose of sunvoertinib were included in the safety analysis. Results: As of October 17, 2022, a total of 32 patients who met efficacy evaluable criteria were included in the analysis. The doses of sunvozertinib ranged from 50 mg - 400 mg. Baseline characteristics: median age was 64.5 years old; 68.8% (22/32) were female; 75.0% (24/32) ECOG PS was 1; 34.4% (11/32) had more than three metastatic sites; 43.8% (14/32) had baseline brain metastases. Patients were heavily pretreated, with a median of 5 lines (range 1 - 16) of prior therapies. All patients had been treated with at least one type of EGFR TKI, including 68.8% (22/32) had been treated with a 3 rd generation EGFR TKI. The majority of patients (29/32, 90.6%) had also been treated with chemotherapy. Anti-tumor activity was observed starting from 50 mg. Per investigators’ assessment, the best objective response rate (BoR) was 21.9% (7/32). Anti-tumor activity was observed regardless of T790M mutation status. At the data cutoff date, the median duration of response and progression-free survival were 4.0 months and 5.9 months, respectively. Sunvozertinib was well-tolerated across all dose levels. The safety profile was similar to what has been previously reported. The longest treatment duration was more than 35 months (still ongoing). Conclusions: Sunvozertinib monotherapy demonstrated promising anti-tumor activity in heavily pretreated EGFRm NSCLC patients. Further clinical evaluation of sunvozertinib in this patient population is warranted. The updated data will be presented at the conference. Clinical trial information: NCT05559645 NCT03974022 and CTR20192097 .
Subtly Increased Focal FDG Activity in the Liver Due to Paragonimiasis
Authors: Jiaona Dai, Haitao Wang, Hui Wang, Rong Tian
Journal: Clinical Nuclear Medicine (2023)

A 32-year-old man underwent 18 F-FDG PET/CT to evaluate suspicious hepatic metastases, which were revealed by ultrasonography and MRI. The FDG PET/CT images demonstrated only one focus of subtly increased activity in the liver without abnormality elsewhere. The pathological result from hepatic biopsy was consistent with Paragonimus westermani infection.
Primary Extraskeletal Ewing Sarcoma of the Duodenum Revealed by 18F-FDG PET/CT
Authors: Hao Liu, Yan Deng, Nan Liu, Jing Huang, Wei Zhang
Journal: Clinical Nuclear Medicine (2023)

Extraskeletal Ewing sarcoma of the duodenum is a relatively uncommon entity tumor. We report a case of extraskeletal Ewing sarcoma in a 21-year-old woman. She complained of abdomen pain and melena. 18 F-FDG PET/CT showed an intense uptake by the duodenum mass along with multiple FDG-avid enlarged lymph nodes in the mesentery, which was pathologically proven as extraskeletal Ewing sarcoma.
Author correction to ‘Approved HIV reverse transcriptase inhibitors in the past decade’ [Acta Pharmaceutica Sinica B 12 (2022) 1567–1590]
Authors: Guangdi Li, Yali Wang, Erik De Clercq
Journal: Acta Pharmaceutica Sinica B (2023)

[This corrects the article DOI: 10.1016/j.apsb.2021.11.009.].
Lifelike Transformative Materials for Biohybrid Implants: Inspired by Nature, Driven by Technology
Authors: Alicia Fernández‐Colino, Fabian Kiessling, Ioana Slabu, Laura De Laporte, Payam Akhyari, Saskia K. Nagel, Julia Stingl, Stefanie Reese, Stefan Jockenhoevel
Journal: Advanced Healthcare Materials (2023)

Today's living world is enriched with a myriad of natural biological designs, shaped by billions of years of evolution. Unraveling the construction rules of living organisms offers the potential to create new materials and systems for biomedicine. From the close examination of living organisms, several concepts emerge: hierarchy, pattern repetition, adaptation, and irreducible complexity. All these aspects must be tackled to develop transformative materials with lifelike behavior. This perspective article highlights recent progress in the development of transformative biohybrid systems for applications in the fields of tissue regeneration and biomedicine. Advances in computational simulations and data-driven predictions are also discussed. These tools enable the virtual high-throughput screening of implant design and performance before committing to fabrication, thus reducing the development time and cost of biomimetic and biohybrid constructs. The ongoing progress of imaging methods also constitutes an essential part of this matter in order to validate the computation models and enable longitudinal monitoring. Finally, the current challenges of lifelike biohybrid materials, including reproducibility, ethical considerations, and translation, are discussed. Advances in the development of lifelike materials will open new biomedical horizons, where perhaps what is currently envisioned as science fiction will become a science-driven reality in the future.
FAP-Targeted 4-1BB Agonist Tamps Down Advanced Tumors
Journal: Cancer Discovery (2023)

Findings from a phase I study of the bispecific antibody RO7122290, which targets CD137 and the fibroblast activity protein, show that it produces responses in patients with advanced solid tumors-without the liver toxicity associated with earlier therapies targeting CD137. Additional research evaluating RO7122290 in combination with atezolizumab or other immune agents is planned.
Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial
Authors: Carolyn T Bramante, John B Buse, David M Liebovitz, Jacinda M Nicklas, Michael A Puskarich, Ken Cohen, Hrishikesh K Belani, Blake J Anderson, Jared D Huling, Christopher J Tignanelli, Jennifer L Thompson, Matthew Pullen, Esteban Lemus Wirtz, Lianne K Siegel, Jennifer L Proper, David J Odde, Nichole R Klatt, Nancy E Sherwood, Sarah M Lindberg, Amy B Karger, Kenneth B Beckman, Spencer M Erickson, Sarah L Fenno, Katrina M Hartman, Michael R Rose, Tanvi Mehta, Barkha Patel, Gwendolyn Griffiths, Neeta S Bhat, Thomas A Murray, David R Boulware, Blake Anderson, Riannon C Atwater, Nandini Avula, Kenny B Beckman, Hrishikesh K Belani, David R Boulware, Carolyn T Bramante, Jannis Brea, Courtney A Broedlow, John B Buse, Paula Campora, Anup Challa, Jill Charles, Grace Christensen, Theresa Christiansen, Ken Cohen, Bo Connelly, Srijani Datta, Nikita Deng, Alex T Dunn, Spencer M Erickson, Faith M Fairbairn, Sarah L Fenno, Daniel J Fraser, Regina D Fricton, Gwen Griffiths, Aubrey A Hagen, Katrina M Hartman, Audrey F Hendrickson, Jared D Huling, Nicholas E Ingraham, Arthur C Jeng, Darrell M Johnson, Amy B Karger, Nichole R Klatt, Erik A Kuehl, Derek D LaBar, Samuel Lee, David M Liebovitz, Sarah Lindberg, Darlette G Luke, Rosario Machicado, Zeinab Mohamud, Thomas A Murray, Rumbidzai Ngonyama, Jacinda M Nicklas, David J Odde, Elliott Parrens, Daniela Parra, Barkha Patel, Jennifer L Proper, Matthew F Pullen, Michael A Puskarich, Via Rao, Neha V Reddy, Naveen Reddy, Katelyn J Rypka, Hanna G Saveraid, Paula Seloadji, Arman Shahriar, Nancy Sherwood, Jamie L Siegart, Lianne K Siegel, Lucas Simmons, Isabella Sinelli, Palak Singh, Andrew Snyder, Maxwell T Stauffer, Jennifer Thompson, Christopher J Tignanelli, Tannon L Tople, Walker J Tordsen, Ray HB Watson, Beiqing Wu, Adnin Zaman, Madeline R Zolik, Lena Zinkl
Journal: The Lancet Infectious Diseases (2023)
Dose-escalated simultaneous integrated boost radiotherapy in early breast cancer (IMPORT HIGH): a multicentre, phase 3, non-inferiority, open-label, randomised controlled trial
Authors: Charlotte E Coles, Joanne S Haviland, Anna M Kirby, Clare L Griffin, Mark A Sydenham, Jenny C Titley, Indrani Bhattacharya, A Murray Brunt, H Y Charlie Chan, Ellen M Donovan, David J Eaton, Marie Emson, Penny Hopwood, Monica L Jefford, Sara V Lightowlers, Elinor J Sawyer, Isabel Syndikus, Yat M Tsang, Nicola I Twyman, John R Yarnold, Judith M Bliss
Journal: The Lancet (2023)
Association of tertiary lymphoid structures with outcomes from PD-1 inhibition in advanced malignant pleural mesothelioma.
Authors: Krisztian Homicsko, Giota Zygoura, Stephanie Tissot, Sanjay Popat, Alessandra Curioni-Fontecedro, Tereza Dellaporta, Mary O'Brien, Anthony Pope, Riyaz N.H. Shah, Rosita Kammler, Stephen P. Finn, George Coukos, Solange Peters, Rolf A. Stahel
Journal: Journal of Clinical Oncology (2023)

e20545 Background: Predictive biomarkers of benefit form immunotherapy in malignant mesothelioma patients remain poorly defined. The 9-15 PROMISE-MESO study (NCT02991482) of the European Thoracic Oncology Platform (ETOP) evaluated second-line pembrolizumab against chemotherapy. Pembrolizumab led to an increased response rate compared to chemotherapy, which did not translate to survival benefits. We evaluated if the presence of tertiary lymphoid structures (TLSs) with different compositions or LRRC15+ immune suppressive fibroblasts could predict the clinical benefit from pembrolizumab. Methods: We performed multiplex immune histochemistry analysis on tumor tissues. 144 patients were included in the clinical trial, from whom, 112 had available tumor tissue for analysis: 55 patients in the chemotherapy arm, and 57 patients in the immune therapy arm. We performed the following panel: calretinin or WT1 (mesothelioma cells), CD20, CD23, CD11c, LRRC15, aSMA, and DAPI. We used the Akoya Vectra Polaris platform for analysis. The IFQuant analytical pipeline developed at the Swiss Institute for Bioinformatics (SIB) was used for analyses. Results: We defined three categories of TLSs: general CD20+ TLSs independent of other markers. CD20/CD23 double-positive as mature TLSs (mTLS), and TLSs with dendritic cells (CD11c+, cTLS). Immune suppressive CAFs were defined as LRRC15+ cells/mm2. CD20+ TLSs were identified in 84% of patients' stroma, with a median of 21 TLSs/tumor tissue and 2 TLSs/mm2. mTLSs were rare, only detected in 10 of the 112 patients (9%). cTLSs with dendritic cells were more frequent and present in 45% of all patients (50/112), and roughly half of the TLS+ patients (53%) had CD11c+ cells detected in TLSs. LRRC15+ cancer-associated fibroblasts (CAFs) were detected in 85% of patients, with a median density of 61 cells/mm2. LRRC15- tumors also contained TLSs but had significantly fewer than LRRC15+ tumors (p = 0.0079). We did not find any significant association between the responses or PFS with TLS, mTLS, and LRRC15+ CAFs. We found inverse association between cTLS levels and response to immune therapy (p = 0.037) but not for PFS. Conclusions: Our data shows that advanced malignant mesotheliomas frequently harbor TLSs, but these TLSs are mostly not activated/mature. The absence of antigen-presenting cells in TLSs, like CD11c dendritic cells, is unexpectedly associated with increased response to pembrolizumab. The high prevalence of immune suppressive LRRC15+ CAFs might explain the low response rate to pembrolizumab and could be linked to the absence of maturation of TLSs. Clinical trial information: EudraCT number: 2016-002062-31 .
AB0629 DEMOGRAPHIC, CLINICAL AND SEROLOGICAL CHARACTERISTICS OF SJÖGREN’S SYNDROME PATIENTS
Authors: H. Baygin, G. Sargin, S. Cildag, T. Senturk
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Sjogren's syndrome (SS); is a chronic multisystem inflammatory autoimmune disease characterized by dry eyes and mouth, involving lymphocytic infiltration of the lacrimal and salivary glands. Glandular involvement and extraglandular symptoms involving various organs and systems can be seen in patients. It can be seen in all age groups, although it is most common in those aged 45-50 years. The average female/male incidence rate is 9/1. <h3>Objectives</h3> Our aim in this study is to present the demographic, clinical and serological characteristics of patients diagnosed with SS. <h3>Methods</h3> Our study included 466 patients diagnosed with SS according to the 2016 ACR/EULAR Classification Criteria. Age, gender, primary/secondary SS status of the patients; organ involvement, salivary gland biopsy and serological features were recorded. Descriptive statistics were given as mean±standard deviation, frequency (n), and percent (%). <h3>Results</h3> The mean age of 466 (433 females, 33 males) patients in the study was 55.4±13.5 years. The female/male ratio was 13/1. There were 408 (87.5%) patients with primary SS diagnosis and 58 (12.5%) patients with secondary SS diagnosis. 67% of patients with a diagnosis of secondary SS had rheumatoid arthritis. The most common clinical presentation complaints were dry eye (86%) and dry mouth (67.8%). In our study, anti-nuclear antibody positivity was found to be 83.4%, rheumatoid factor positivity was 22.1%. Ro-52 antibody was positive in 56.4% of the patients. As a result of the evaluation in terms of organ/system involvement; pulmonary involvement was found in 45 patients (9.6%). Moreover; primary biliary cirrhosis in 18 (3.8%) patients, adrenal insufficiency in 1 (0.2%) patient, chronic tubulointerstitial nephritis in 2 (0.4%) patients, crescentic glomerulonephritis in 1 (0.2%) patient, optic neuropathy was found in 1 (0.4%) patient, and lymphoma was found in 1 (0.2%) patient (Table 1). <h3>Conclusion</h3> Sjögren's syndrome can affect almost any organ system, thus various systemic manifestations may occur. The disease is characterized by pleomorphic clinical manifestations, which can vary greatly in features and severity from one patient to another. Diagnosis of the disease is based on characteristic clinical signs and symptoms as well as specific tests including salivary gland histopathology and autoantibodies. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS1189-HPR LUNG AND MYELOPROLIFERATIVE NEOPLASMS IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH JANUS KINASE INHIBITORS: A REVIEW OF THE LITERATURE
Authors: O. Hamdi, M. Yasmine, S. Miladi, F. Alia, H. Boussaa, L. Souabni, K. Ouenniche, S. Kassab, S. Chekili, K. Ben Abdelghani, A. Laatar
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Janus Kinase inhibitors (JAKi) have been shown to be effective in the therapeutic strategy of rheumatoid arthritis (RA). However, an increased risk of developing malignancy has been reported in previous literature [1]. <h3>Objectives</h3> This review aimed to investigate the risk of lung carcinoma and subsequent myeloproliferative neoplasm (MPN) in RA patients treated with JAKi. <h3>Methods</h3> We conducted a literature review in order to identify cases of lung carcinoma and MPN associated to JAKi in RA patients. A comprehensive search was conducted using <i>PubMed</i> and <i>Scopus</i>. The databases were searched from 2015 until date December 2022. No restrictions were applied in terms of study design, setting, country, or time frame. For <i>PubMed</i>, the search was carried out using a strategy employing the combination of synonyms of "pulmonary neoplasm", terms related to "JAK inhibitors", and terms related to "rheumatoid arthritis". For Scopus, the previous terms were searched in the article title, abstract, or key-words. We also did manual research on reference lists of retrieved relevant articles. Articles were eliminated if they had duplicate titles, did not contain the key-words, or included the words "review", "expert's opinion", or "qualitative". In this review, we included prospective or retrospective case reports and case series conducted on JAKi and lung carcinoma or MPN. <h3>Results</h3> The initial search yielded 153 papers. Following duplicate elimination, we screened for 119 papers. Only eight papers were finally selected for analysis and met inclusion criteria. The mean number of RA patients included was 2422 [486-6194]. Standardized incidence ratio of lung carcinoma and MPN ranged from 0.17 to 0.19 and 0.01 to 0.1, respectively. Most papers raised the possibility that RA patients treated with JAKi may have a markedly higher rate of development of lung carcinoma (95% CI [1.51 - 1.79]) or MPN (95% CI [2.05 - 2.96]) compared to patients who did not receive the treatment. The Table 1 exposes the main characteristics of the nine studies retained in this review. <h3>Conclusion</h3> Our study showed that JAKi was associated with an increased risk of development of lung malignancy and lymphoma. Although the risk of malignancy is increased compared with the general population, it is still similar to that seen in the overall RA patients. <h3>Reference</h3> [1] Curtis JR, Lee EB, Kaplan IV, et al. Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme. Ann Rheum Dis 2016;75(5):831–41 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
Practical thematic analysis: a guide for multidisciplinary health services research teams engaging in qualitative analysis
Authors: Catherine H Saunders, Ailyn Sierpe, Christian von Plessen, Alice M Kennedy, Laura C Leviton, Steven L Bernstein, Jenaya Goldwag, Joel R King, Christine M Marx, Jacqueline A Pogue, Richard K Saunders, Aricca Van Citters, Renata W Yen, Glyn Elwyn, JoAnna K Leyenaar
Journal: BMJ (2023)

Qualitative research methods explore and provide deep contextual understanding of real world issues, including people's beliefs, perspectives, and experiences. Whether through analysis of interviews, focus groups, structured observation, or multimedia data, qualitative methods offer unique insights in applied health services research that other approaches cannot deliver. However, many clinicians and researchers hesitate to use these methods, or might not use them effectively, which can leave relevant areas of inquiry inadequately explored. Thematic analysis is one of the most common and flexible methods to examine qualitative data collected in health services research. This article offers practical thematic analysis as a step-by-step approach to qualitative analysis for health services researchers, with a focus on accessibility for patients, care partners, clinicians, and others new to thematic analysis. Along with detailed instructions covering three steps of reading, coding, and theming, the article includes additional novel and practical guidance on how to draft effective codes, conduct a thematic analysis session, and develop meaningful themes. This approach aims to improve consistency and rigor in thematic analysis, while also making this method more accessible for multidisciplinary research teams.